Prevention of Renal Failure by Nitric Oxide in Prolonged Cardiopulmonary Bypass.
- Conditions
- Cardiac Valve Replacement ComplicationHeart Valve DiseasesHeart; Complications, Valve, Prosthesis
- Interventions
- Other: inhaled NitrogenOther: inhaled nitric oxide
- Registration Number
- NCT01802619
- Lead Sponsor
- Xijing Hospital
- Brief Summary
Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging.
- Detailed Description
Prolonged periods of cardiopulmonary bypass (CPB) cause high levels of plasma free haemoglobin(Hb) and are associated with increased morbidity. We hypothesized that repletion of nitric oxide (NO) during and after the surgical procedure on CPB may protect against endothelium dysfunction and organ failure caused by plasma-Hb induced NO scavenging. There are three possible beneficial mechanisms of delivering NO:
1. Nitric oxide reduces ischemia-reperfusion injury (such as in acute myocardial infarction, stroke, and acute tubular necrosis).
2. Nitric oxide has anti-inflammatory properties. As antioxidants, exogenous NO may reduce injury by counteracting the cytotoxic effects of reactive oxygen species, modulating leukocyte recruitment, edema formation and tissue disruption.
3. Exogenous nitric oxide prevents noxious effects of hemolysis-associated NO dysregulation. During hemolysis, nitric oxide gas oxidized of plasma oxyhemoglobin to methemoglobin, thereby inhibiting endogenous endothelium NO scavenging by cell-free Hb.
NO depletion during hemolysis and its sequelae. The release of plasma free Hb (with Fe2+ iron) by hemolysis avidly scavenges nitric oxide (NO) by the dioxygenation reaction. Elevated plasma ferrous Hb levels can induce a "NO deficiency" state. Reduced vascular nitric oxide levels can contribute to vasoconstriction, inflammation, and thrombosis, potentially contributing to systemic endothelial dysfunction after cardiac surgery with CPB.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 217
- Provide written informed consent
- Are > 18 years of age
- Elective cardiac or aortic surgery with CPB, when the surgeon plans double valve replacement.
- Stable pre-operative renal function, without dialysis.
- Emergent cardiac surgery
- Life expectancy < 1 year
- Hemodynamic instability as defined by a systolic blood pressure <90 mmHg
- Administration of ≥1 Packed Red Blood Cell transfusion in the week before surgery
- X-ray contrast infusion less than 1 week before surgery
- Anticipate administration of nephrotoxic agents, such as hydroxyethyl starch
- Evidence of intravascular or extravascular hemolysis
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description inhaled nitrogen inhaled Nitrogen Using an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, pure nitrogen (placebo) is mixed with pure O2 or air. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the NO is delivered through the inspiratory limb of the anesthetic or ventilator circuit. inhaled nitric oxide inhaled nitric oxide Using an Inovent (Ikaria Inc, N.J., USA) or volumetrically-calibrated flowmeters, 800 ppm NO gas is mixed with pure O2 or air to obtain a final concentration of 80 ppm NO. During CPB the gas mixture is delivered through the extracorporeal oxygenator, after CPB the gas is delivered through the inspiratory limb of the anesthetic or ventilator circuit. NO, NO2 and O2 and methemoglobin levels are monitored by an unblinded observer.
- Primary Outcome Measures
Name Time Method acute kidney injury an increase of serum creatinine by 50% within 7 days after surgery, or an increase of serum creatinine by 0.3 mg/dl within 2 days after surgery acute kidney injury was defined by the KDIGO criteria
- Secondary Outcome Measures
Name Time Method Chronic kidney disease at 30 days, 90 days, and 1 year following ICU admission defined as eGFR\<60 mL/min/1.73m2
Incidence of nonfatal stroke and nonfatal myocardial infarction. at 30 days, 90 days, and 1 year following ICU admission Nonfatal stroke will be assessed by the NIH Stroke Scale at baseline before surgery and at 28 days, 60 days, 90 days and 1 year after surgery.
Nonfatal myocardial infarction is defined by the third universal definition of MI released in 2012 by the ESC/ACCF/AHA/WHF.Major adverse kidney events (MAKE) at 30 days, 90 days, and 1 year following ICU admission a composite outcome of loss of 25% of eGFR from baseline, end stage renal disease requiring a continuous renal replacement therapy and mortality.
Renal Replacement Therapy at 30 days, 90 days, and 1 year following ICU admission the incidence of need for Renal Replacement Therapy
Loss of 25% of eGFR compared to baseline at 30 days, 90 days, and 1 year following ICU admission Loss of 25% of eGFR compared to baseline
Quality of life at 30 days, 90 days, and 1 year following ICU admission The quality of life will be evaluated by the Katz Index of In dependence in Activities of Daily living
overall mortality at 30 days, 90 days, and 1 year following ICU admission all cause mortality
Trial Locations
- Locations (1)
Xijing Hospital
🇨🇳Xi'an, Shaanxi, China